Acute Renal Failure (ARF) is said to occur in anywhere from 1% to 25% of critically ill patients and mortality in these populations ranges from 28% to 90%. Most definitions of ARF have common elements, including the use of serum creatinine and urine volume. Although the kidney has numerous functions, these are the only functions that are routinely and easily measured and that are unique to the kidney. The accuracy of a creatinine clearance measurement even under the best circumstances is limited because as glomerular filtration rate (GFR; a measure of kidney function) falls creatinine secretion is increased, and thus the rise in serum creatinine is attenuated.
Thus, creatinine excretion is much greater than the actual filtered urine load, resulting in a potentially large overestimation of the GFR (as much as a twofold difference) and erroneous assumptions regarding kidney function by clinicians. In addition, plasma creatinine concentrations only rise if greater than 50% of the normal GFR is lost, making GFR an unreliable and very insensitive marker of kidney failure and causing delays in diagnosis well beyond 24 hours post-surgery. Nevertheless, serum creatinine remains the key kidney-specific biomarker used to determine whether renal function is improving, declining, or stabilizing. Like creatinine clearance, the serum creatinine will not be an accurate reflection of GFR in the non-steady-state condition of ARF. Urine output is far less specific than serum creatinine for determination of kidney function, except when urine output is severely decreased or absent. Severe ARF can exist despite normal urine output (i.e., nonoliguric) but changes in urine output can occur long before biochemical changes are apparent.
The wide variety of definitions of ARF used in clinical practice in the past led to the formation of the Acute Dialysis Quality Inititative (ADQI) workgroup and publication of a consensus definition based on RIFLE criteria which are based solely on changes in serum creatinine and urine output. The RIFLE criteria allow for three classifications of increasing severity of kidney injury, including Risk, Injury, and Failure, and two outcome criteria, Loss, and End Stage Renal Disease or ESRD (Bellomo R., et al., 2004 Crit. Care 8: 204-12). The efficacy of the RIFLE criteria have been examined and shown to be a useful classification system for classifying kidney injury (Uchino S, et al., 2005, JAMA 294: 813-18).
Acute kidney injury (AKI) is a common and severe complication in hospitalized patients and is associated with increased morbidity and mortality. Cardiac disease and cardiac surgery are both common causes of AKI. In critically ill patients cardiac surgery with cardiopulmonary bypass (CPB) is the second most common cause of AKI. This condition can be classified as a form of cardiorenal syndrome (CRS) type 1, characterized by an abrupt worsening of renal function secondary to acute cardiac disease or procedures. Cardiac surgery associated AKI is a particular type of type 1 CRS for which no clear understanding of pathogenesis exists and no proven, effective prophylaxis or treatment is yet identified. Furthermore, existing renal markers, which confirm loss of renal function in this setting, are only very late markers, for the diagnosis of AKI late in the course of the problem.